Previous studies of cocaine dependence have sought to identify predictors of a positive treatment response, and have focused on personality traits, cognitive ability, and co-morbidity. In the first cycle of this award, our group investigated the rle of neurochemistry in success and failure to respond to a well-established behavioral treatment for cocaine dependence. Using Positron Emission Tomography (PET) and the radiotracer [11C]raclopride, we measured both D2/3 receptor binding potential (BPND) and stimulant-induced [11C]raclopride displacement (BPND) in treatment-seeking cocaine dependent subjects. The scans were performed prior to subjects receiving a behavioral treatment that uses positive reinforcement (voucher incentives) for 24 weeks. The results showed that both PET outcome measures were increased in the subjects who responded to treatment compared to those who relapsed. In addition, both BPND and BPND did not differ between the treatment responders and a group of matched healthy controls. Thus, these results suggest that low dopamine transmission is associated with a greater likelihood of a poor treatment response, and that treatment responders may have intact dopamine signaling. The goal of this competing renewal is to use imaging to further expand our understanding of the deficit of dopamine transmission seen in treatment non-responders. The first goal will be to replicate the finding seen in cycle one with [11C]raclopride and a stimulant challenge. In order to better characterize the deficit in dopamine signaling, PET scans will be also performed with the radiotracer [18F]DOPA, which provides a measure of pre-synaptic dopamine synthesis and storage. In addition, fMRI scans will be performed to probe the reward system. Combined, these imaging studies will provide an understanding of the differences in striatal dopamine transmission and activation of reward pathways that differentiate cocaine dependent subjects who respond to treatment compared to those who relapse, and can be used to direct future treatment development.